Diabetic Postmenopausal Women Research Articles

The effect of Aerobic training on Klotho-FGF23 axis and arterial calcification in type 2 diabetic Postmenopausal women

مقدمه: هر چند انجام فعالیت ورزشی یکی از راهکارهای کمک درمانی در کاهش سختی شریانی در بیماران دیابتی است اما، سازوکار آن معلوم نیست. هدف از این پژوهش تعیین اثر فعالیت هوازی بر محور کلوتو- عامل رشدی فیبروبلاست 23 (FGF23) و کلسیمی شدن شریان در زنان یائسه دیابتی نوع ۲ بود.روش‌ها: 24 نفر زن یائسه دیابتی نوع-۲ از انجمن دیابت شهر شاهرود به ‌صورت تصادفی به دو گروه: ۱) تمرین ]۱۲ نفر[ با میانگین سنی ۶±۵۱ سال و توده بدن ۵ ± ۹/۳۱ kg/m2 و ۲) کنترل ]۱۲ نفر[ با میانگین‌ سنی ۵±۵۲ سال و توده بدن ۸/۳ ± ۲/۲۹ kg/m2 تقسیم شدند. تمرینات هوازی شامل ۳ جلسه در هفته به مدت ۸ هفته و هر جلسه ۴۵ الی ۶۰ دقیقه دویدن روی تردمیل با شدت ۷۰-۴۵ درصد ضربان قلب ذخیره بود. نمونه خون، قبل و پس از دوره تمرین در حالت ناشتا گرفته شد و برای اندازه‌گیری کلوتو و FGF23 از روش الایزا استفاده شد. همچنین آزمون سختی شریان‌ها و فشار‌خون با استفاده از سیستم VaSera-VS-2000 انجام شد. داده­ها با استفاده از آزمون‌های تی وابسته و مستقل (۰۵/۰>P) آنالیز شدند.یافته‌ها: تغییر معنی­داری در فسفر، FGF23، حاصل‌ضرب کلسیم در فسفر، فشارخون دیاستول و حداکثر اکسیژن مصرفی در طی دوره تحقیق مشاهده نشد (۰۵/۰ P). همچنین فشارخون سیستولیک، نسبت کلوتو به FGF23 و سختی شریانی در گروه تجربی نسبت به گروه کنترل به‌طور معنی­داری کاهش و کلوتو به‌طور معنی‌داری افزایش یافت (۰۵/۰>P).نتیجه‌گیری: تمرینات هوازی می‌تواند باعث کاهش سختی عروقی در زنان یائسه مبتلا به دیابت نوع ۲ شود، که بوسیله فاکتورهای مرتبط با کلوتو، نسبت کلوتو به FGF23 و فشارخون تحقق می‌یابد. با این حال، با توجه به تحقیقات بسیار کم در این زمینه، نیاز است این یافته‌ها در تحقیقات آتی بررسی و تائید گردند.

Post-Menopausal Sex Hormones in Relation to Type 2 Diabetes Mellitus

Sex Hormone binding globulin is a glyco protein that transports the sex steroids to their target tissue. The concentration of free steroids in the circulation depends upon the availability of serum SHBG. Low SHBG is associated with hyperinsulinemia, T2DM, and cardiovascular risk. Objective: The objective of the study was to determine the correlation of SHBG with hormone levels, insulin and BMI in post- menopausal women with type 2 diabetes mellitus (T2DM). Research Design and methods: One hundred and five post menopausal women with diabetes and eighty five postmenopausal women without diabetes were recruited for the study. Height, weight, BMI, was measured. Insulin,SHBG and sex steroids were measured by enzyme linked immunosorbent assay (ELISA). Results: The mean concentration of SHBG was higher in control group 25.21 (16.1- 43.7), than the diabetic postmenopausal women 20.65 (12.54-33.46) p<0.05. A significant inverse association was observed between insulin resistance, free testosterone and BMI. Conclusion: In postmenopausal women with type 2 diabetes mellitus low levels of SHBG is observed which shows an inverse correlation with insulin resistance, free testosterone and DHEA leading to hyperandrogenecity and hyperinsulinemia .

Association of oxidative stress with the bone turnover in pre and post menopausal diabetic women

Diabetes is today a worldwide problem because of its global prevalence. India is also one of the hub. The long term complications of diabetes have been extensively studied but it has been observed that diabetes also affects the bone health. The relation of Bone health, Oxidative stress and diabetes has not been looked into to a great extent. To study the relation of Bone health, Oxidative stress in diabetic individuals.330 individuals were included in the study. Dividing into four group i.e group I included Pre Menopausal type II DM (n=80), group II was age matched control (n=75), group III were Post Menopausal type II DM (n=100) and group IV (n=75) were age matched Post Menopausal control group. The protocol of the study was approved by ethical committee of the institute. GHbA1C, Osteocalcin, TRAP, Alkaline Phosphatase, SOD, GSH, GPx, Gred, MDA and Minerals like Calcium, Phosphorous, Magnesium were estimated.A highly significant increase (p<0.0001) in levels of MDA and antioxidants (SOD,GSH, GPx, Gred) was observed in the premenopausal women while through MDA levels were high in the menopausal women. While the altered levels of the bone markers were observed. Sr TRAP as the marker of bone resoption was increased significantly (p<0.0001) in pre but not significant in the post menopausal group while Sr Osteocalcin and Sr Alkaline phosphatase markers of bone formation was low in pre and not significant variation observed in the post menopausal women.The Oxidative stress, hyperglycemia and the decreased antioxidant defense leads to enhanced osteoclastic activity and a decreased osteoblastic activity in pre and post menopausal diabetic women.

MiR-1908/EXO1 and MiR-203a/FOS, regulated by scd1, are associated with fracture risk and bone health in postmenopausal diabetic women.

Background: Stearoyl–coenzyme A desaturase-1 (SCD1) can inhibit the development of diabetic bone disease by promoting osteogenesis. In this study, we examined whether this regulation by SCD1 is achieved by regulating the expression of related miRNAs.Methods: SCD1 expression levels were observed in human bone-marrow mesenchymal stem cells (BM-MSCs) of patients with type 2 diabetes mellitus (T2DM), and the effect of SCD1 on osteogenesis was observed in human adipose-derived MSCs transfected with the SCD1 lentiviral system. We designed a bioinformatics prediction model to select important differentially expressed miRNAs, and established protein–protein interaction and miRNA–mRNA networks. miRNAs and mRNAs were extracted and their differential expression was detected. The SCD1–miRNA–mRNA network was validated.Findings: SCD1 expression in bone marrow was downregulated in patients with T2DM and low-energy fracture, and SCD1 expression promotes BM-MSC osteogenic differentiation. The predictors in the nomogram were seven microRNAs, including hsa-miR-1908 and hsa-miR-203a. SCD1 inhibited the expression of CDKN1A and FOS, but promoted the expression of EXO1 and PLS1. miR-1908 was a regulator of EXO1 expression, and miR-203a was a regulator of FOS expression.Interpretation: The regulation of BM-MSCs by SCD1 is a necessary condition for osteogenesis through the miR-203a/FOS and miR-1908/EXO1 regulatory pathways.

Dietary Manganese, Plasma Markers of Inflammation, and the Development of Type 2 Diabetes in Postmenopausal Women: Findings From the Women's Health Initiative.

To examine the association between manganese intake and the risk of type 2 diabetes in postmenopausal women and determine whether this association is mediated by circulating markers of inflammation. We included 84,285 postmenopausal women without a history of diabetes from the national Women's Health Initiative Observational Study (WHI-OS). Replication analysis was then conducted among 62,338 women who participated in the WHI-Clinical Trial (WHI-CT). Additionally, data from a case-control study of 3,749 women nested in the WHI-OS with information on biomarkers of inflammation and endothelial dysfunction were examined using mediation analysis to determine the relative contributions of these known biomarkers by which manganese affects type 2 diabetes risk. Compared with the lowest quintile of energy-adjusted dietary manganese, WHI-OS participants in the highest quintile had a 30% lower risk of type 2 diabetes (hazard ratio [HR] 0.70 [95% CI 0.65, 0.76]). A consistent association was also confirmed in the WHI-CT (HR 0.79 [95% CI 0.73, 0.85]). In the nested case-control study, higher energy-adjusted dietary manganese was associated with lower circulating levels of inflammatory biomarkers that significantly mediated the association between dietary manganese and type 2 diabetes risk. Specifically, 19% and 12% of type 2 diabetes risk due to manganese were mediated through interleukin 6 and hs-CRP, respectively. Higher intake of manganese was directly associated with a lower type 2 diabetes risk independent of known risk factors. This association may be partially mediated by inflammatory biomarkers.

Comparison of the effect of different anti-diabetic therapy on bone profiles in postmenopausal women

A total of 81 postmenopausal women aged 50 years or older were recruited. Patients with type 2 diabetes mellitus were classified into 3 groups: women on metformin monotherapy (M, n = 20), women on metformin and insulin therapy (M + I, n = 28) and women on insulin monotherapy (I, n = 25). A group of women without treatments of diabetes was included (WT, n = 8). Biochemical analysis was obtained and BMD, BMC, lean and fat mass in different sites were measured by dual-energy X-ray absorptiometry scanning. The results show a significantly higher femoral neck BMD value in women on metformin combined to insulin therapy compared to women on insulin monotherapy after adjustment for all possible covariates. In addition, we observed a higher BMC at the trunk level in women taking metformin drugs compared to those taking insulin combined with metformin treatment, and between women on insulin and metformin drugs compared to those on insulin injection after adjustment. However, there is no significant difference in bone markers concentrations between groups. We hypothesized that only insulin monotherapy is associated to a reduced bone mineral density and content in type 2 diabetic postmenopausal women.

Combined Aerobic and Resistance Exercise Training Reduces Circulating Apolipoprotein J Levels and Improves Insulin Resistance in Postmenopausal Diabetic Women.

BackgroundCirculating apolipoprotein J (ApoJ) is closely associated with insulin resistance; however, the effect of exercise on circulating ApoJ levels and the association of ApoJ with metabolic indices remain unknown. Here, we investigated whether a combined exercise can alter the circulating ApoJ level, and whether these changes are associated with metabolic indices in patients with type 2 diabetes mellitus.MethodsPostmenopausal women with type 2 diabetes mellitus were randomly assigned into either an exercise (EXE, n=30) or control (CON, n=15) group. Participants in the EXE group were enrolled in a 12-week program consisting of a combination of aerobic and resistance exercises. At baseline, 4, 8, and 12 weeks, body composition and metabolic parameters including homeostatic model assessment of insulin resistance (HOMA-IR) and serum ApoJ levels were assessed.ResultsIn the EXE group, ApoJ levels decreased 26.3% and 19.4%, relative to baseline, at 8 and 12 weeks, respectively. Between-group differences were significant at 8 and 12 weeks (P<0.05 and P<0.001, respectively). In the EXE group, 12 weeks of exercise resulted in significant decreases in body weight, percent body fat, and HOMA-IR indices. Concurrently, weight-adjusted appendicular skeletal muscle mass (ASM/wt) was increased in the EXE group compared with the CON group. Importantly, changes in the ApoJ level were significantly correlated with changes in ASM/wt.ConclusionExercise training resulted in a significant decrease in the circulating ApoJ level, with changes in ApoJ associated with an improvement in some insulin resistance indices. These data suggest that circulating ApoJ may be a useful metabolic marker for assessing the effects of exercise on insulin resistance.

Type 2 Diabetes Mellitus and Menopausal Hormone Therapy: An Update.

During menopausal transition, various phenotypical and metabolic changes occur, affecting body weight, adipose tissue distribution and energy expenditure as well as insulin secretion and sensitivity. Taken together, these can predispose women to the development of type 2 diabetes mellitus (T2DM). Many women in midlife experience climacteric symptoms, including hot flashes and night sweats. Menopausal hormone therapy (MHT) is then indicated. MHT has a favourable effect on glucose homeostasis in both women without and with T2DM. T2DM was considered in the past as a cardiovascular disease (CVD) equivalent, which would suggest that women with T2DM should not receive MHT. This notion may still deter many clinicians from prescribing MHT to these patients. However, nowadays there is strong evidence to support an individualised approach after careful evaluation of CVD risk. In older women with T2DM (> 60 years old or > 10 years in menopause), MHT should not be initiated, because it may destabilise mature atherosclerotic plaques, resulting in thrombotic episodes. In obese women with T2DM or in women with moderate CVD risk, transdermal 17β-oestradiol could be used. This route of delivery presents beneficial effects regarding triglyceride concentrations and coagulation factors. In peri- or recently post-menopausal diabetic women with low risk for CVD, oral oestrogens can be used, since they exhibit stronger beneficial effects on glucose and lipid profiles. In any case, a progestogen with neutral effects on glucose metabolism should be used, such as natural progesterone, dydrogesterone or transdermal norethisterone. The goal is to maximise benefits and minimise adverse effects.

The Impact of Serum C-peptide Level on Bone Mineral Density in Postmenopausal Type 2 Diabetic Women.

Objective: Recent studies suggested that c-peptide had biological activity on bone metabolism. We aimed to evaluate the impact of c-peptide level on bone mineral density (BMD) in postmenopausal type 2 diabetic women.&#x0D; Methods: Thirty-five insulin naïve type 2 diabetic postmenopausal women were included in our prospective cohort study. Fasting and random c-peptide, parathyroid hormone (PTH), vitamin D, insulin, alkaline phosphatase level (ALP) levels and BMD were evaluated.&#x0D; Results: The mean age of patients was 61.8±8.56 years. The mean fasting c-peptide, random c-peptide and insulin levels were 3.0±1.24, 7.7±3.7 and 13.9±11.2 µIU/ml, respectively. The mean femoral neck (FN-BMD) and total lumbar spine bone mineral density (L-BMD) were 0.787±0.127 and 0.919±0.122 g/cm2, respectively. C-peptide level was associated with total hip BMD (p&lt;0.05) but this relation disappeared after regression analysis adjusted for confounders. A negative correlation between PTH level and FN-BMD was found (p=0.01). Total hip BMD and L-BMD were negatively correlated with age (p=0.01 and p=0.02, respectively). A positive association between DPP4 inhibitor treatment and total hip BMD was observed (p=0.03).&#x0D; Conclusions: We observed a positive association between total hip BMD and serum c-peptide level. However, this relationship disappeared in multiple linear regression analysis. Further studies are necessary to evaluate the impact of c-peptide level on the risk of osteoporosis in T2DM.

Associations of serum sex hormone binding globulin with bone mineral densities and higher 10-year probability of fractures in postmenopausal women with type 2 diabetes mellitus.

Postmenopause and type 2 diabetes mellitus (T2DM) are associated with higher fracture risk. Sex hormones are important in maintaining woman skeleton health. The relationships of sex hormone(s) with bone mineral density (BMD) and fracture risk are still unclear in diabetic-postmenopausal women. This study aimed to investigate the relationships of sex hormones with BMDs and fracture risk in postmenopausal women with T2DM. Two hundred and fourteen postmenopausal women with T2DM were included. BMDs at lumbar spine (L2-4), femoral neck (FN) and total hip (TH) were measured by dual-energy X-ray absorptiometry (DXA). The 10-year probability of fractures was accessed by modified fracture risk algorithm (FRAX) tool. Serum concentrations of sex hormones were measured. Sex hormone binding globulin (SHBG) was a determinant of BMDs at L2-4 (β=-0.199, P<0.05), TH (β=-0.233, P<0.05), major osteoporotic fracture (MOF) (β=0.253, P<0.001) and hip fracture (HF) (β=0.262, P<0.001). Per SD increase in SHBG caused a 2% increase in the risk of osteoporosis/osteopenia. SHBG in quartile-4 was associated with 4.21 higher risk of osteoporosis/osteopenia compared with SHBG in quartile-1. In postmenopausal women with T2DM, higher serum SHBG tended to be associated with lower BMDs, and increased the risk of osteoporosis/osteopenia and the fracture risk.

Incident Fracture Risk in Type 2 Diabetic Postmenopausal Women in Mainland China: Peking Vertebral Fracture Study.

Using data from the Peking Vertebral Fracture Study, we conducted a longitudinal cohort study to investigate the association between type 2 diabetes mellitus (T2DM) and the risk of incident fractures, especially of vertebral fractures (VFs), and we also examined the modifying effect of body mass index (BMI) on this association and the effect of bone mineral density (BMD) T-score as a risk factor for incident fractures in T2DM. Chinese postmenopausal women were enrolled (n = 982), among whom 186 had T2DM. Incident VFs were confirmed by lateral radiographs of the thoracolumbar spine (T4-L5), while incident clinical non-VFs were self-reported. BMDs at the lumbar spine (LS) and femoral neck (FN) were measured by dual-energy X-ray absorptiometry. T2DM and non-DM women were at similar risk for VFs (OR 0.74, 95% CI 0.32-1.74), even adjusting for age, BMI, BMD, and previous fractures. Meanwhile, T2DM women had nearly twice the risk for non-VFs (HR 1.95, 95% CI 1.11-3.35) compared with non-DM women. After stratifying by BMI, the risk of VFs remained similar between diabetics and non-diabetics despite their BMI status (p for interaction = 0.470), and the risk of non-VFs was positively associated with T2DM only in women with BMI ≥ 25kg/m2 (HR 3.59, 95% CI 1.68-7.65) (p for interaction = 0.065). Although LS BMD T-score was similarly and negatively associated with incident VFs both in T2DM (OR 0.34, 95% CI 0.12-0.88) and non-DM women (OR 0.60, 95% CI 0.44-0.82) (p for interaction = 0.430), the FN BMD T-score was not found to be significantly associated with either non-VFs or VFs among T2DM women. Comparing T2DM and non-DM women with similar fracture risks, the mean difference in LS T-score was - 0.36 (95% CI - 1.77 to 1.04) for VF, and difference in FN T-score was 1.61 (95% CI - 0.11 to 3.34) for non-VF. In conclusion, Chinese postmenopausal women with T2DM had a similar risk of incident VFs, but a significantly higher risk of incident non-VF, compared to women without DM. Higher BMI did not modify the effect of T2DM on risk of VFs, but it increased the association between T2DM and risk of non-VFs. LS BMD T-score was similarly and negatively associated with VF risk in T2DM and non-DM women and appear to be useful for clinical evaluation of VF risk.

Gonadotropins and Their Association with the Risk of Prediabetes and Type 2 Diabetes in Middle-Aged Postmenopausal Women.

Recent studies have suggested that a low concentration of follicle-stimulating hormone (FSH) is associated with a higher prevalence of metabolic disturbances in postmenopausal women. In this study, we aim to evaluate the association between FSH, luteinizing hormone (LH), and LH/FSH ratio values and the risk of insulin resistance (HOMA-IR >2.0), prediabetes (IFG), and type 2 diabetes in a 5-year prospective study in postmenopausal women. 114 postmenopausal women were divided into 4 groups: group 1 (baseline and follow-up normoglycemic women), group 2 (normoglycemic women at baseline progressing to IFG), group 3 (women with baseline and follow-up IFG), and group 4 (women with baseline IFG progressing to diabetes). Baseline and follow-up anthropometric measurements and blood collections were performed. Serum/plasma was assayed for glucose, HDL-C, TG, C-reactive protein (CRP), 17beta-estradiol, estrone, insulin, thyroid-stimulating hormone (TSH), FSH, and LH. Homeostatic model assessment of insulin resistance (HOMA-IR) and LH/FSH ratios were calculated. The baseline concentrations of FSH and LH statistically decreased across all four groups (the highest concentrations in group 1 and the lowest in group 4; p < 0.001). A logistic regression analysis showed that a 1 SD decrease in the z-score of FSH concentration is associated with a threefold increased risk of IFG and a fivefold increased risk of HOMA-IR of >2.0 and diabetes. The LH concentration had odds ratio (OR) values about two times lower than the FSH concentration. The ORs of the LH/FSH ratio were only significant for IFG. In conclusion, FSH concentration is strongly associated with insulin resistance, prediabetes, and diabetes in postmenopausal women with normal or impaired fasting glucose. LH and the LH/FSH ratio are also related to metabolic disturbances after menopause, yet to a lesser extent.

Impact Metformin and Insulin Therapy on Parathyroid Hormone and 25 (OH) Vitamin D in Diabetic Post-menopausal Iraqi Women

The aim of this study is to evaluate the effects of insulin therapy and metformin on parathyroid hormone (PTH), 25 (OH) Vitamin D and alkaline phosphatase activity (ALP) in diabetic post-menopausal women. In this case-control study, 200 individuals were divided into 4 groups each group containing 50 patients, (CG) group were healthy post-menopausal, (OP) group were post-menopausal with osteoporosis (OP), (T2D insulin) group were post-menopausal with diabetic and treated insulin once daily and (T2D-metformin) group were post-menopausal with diabetic and treated metformin (500 mg) twice daily. The results revealed that serum for fasting blood glucose (F.B.G), hemostatic model assessment-insulin resistance (HOMO-RI), 25(OH) Vitamin D, and ALP demonstrated a significant different in (T2D-insulin and T2D-metformin) group comparison with (OP) group. Whereas, the serum PTH, and total calcium was a significant reduce in (T2D-insulin and T2D-metformin) group comparison with (OP) group. Furthermore, the inorganic phosphate non-significant decrees in (T2D-insulin and T2D-metformin) group comparison with (OP) group. The final concluded that insulin therapy increases bone turnover biomarkers more than metformin therapy.

Lipid and glucose metabolism during the menopausal transition & beyond

Transition to menopause, characterized by estrogen decline, is associated with increase in body weight and central adiposity. Moreover, energy expenditure is decreased, as a result of mood changes, comorbidity and inactivity. Insulin secretion and action may also be affected. All these metabolic alterations increase the risk of Type 2 diabetes mellitus. LDL-cholesterol and triglyceride levels increase, while HDL-cholesterol levels decrease during the transition to menopause. Oral estrogens have a decreasing effect on LDL-cholesterol, however, they may increase triglyceride levels. Transdermal estrogens have a more neutral effect on lipid levels. Menopausal Hormone Therapy (MHT) has a favorable effect on glucose homeostasis both in women with and without diabetes. In peri- or recently postmenopausal diabetic women with low cardiovascular risk, oral estrogens may be used, as they have a more beneficial effect on glucose homeostasis. In obese women or in women with moderate cardiovascular risk, transdermal 17β estradiol combined with a metabolically neutral progestogen is the best option. In older women with long - standing diabetes, MHT should rather not be initiated, as therapy may destabilize mature atherosclerotic plaques, leading to thrombotic episodes. Lifestyle intervention, including diet and exercise, is the cornerstone of cardiometabolic prevention in women after menopause.

Multiple pregnancies and the risk of diabetes mellitus in postmenopausal women.

We aimed to investigate whether the number of pregnancies during childbearing age was associated with diabetes in postmenopausal women with no history of gestational diabetes. Our data source was the continuous National Health and Nutrition Examination Survey 1999 to 2014. We selected 9,138 postmenopausal women over 40 years old who did not have a history of gestational diabetes during pregnancy. Logistic regression analyses were applied for the association of the number of pregnancies with diabetes. We found women with ≥4 pregnancies had significantly greater fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), 2-hour plasma glucose, and the Homeostatic Model Assessment of Insulin Resistance than those with two to three pregnancies (all P < 0.01). These women also had a significantly higher prevalence of diabetes (28.4% vs 20.7%; P < 0.001). Using the two to three pregnancies group as the reference, we observed a positive association of log-FPG and log-HbA1c with 4 or more pregnancies after adjustment for sociodemographic, lifestyle, and reproductive factors, and body mass index (both P < 0.05). Compared to women with two to three pregnancies, the odds ratios for diabetes were 1.31 (95% confidence interval [CI] 1.01-1.71) for women who never got pregnant and 1.28 (95% CI 1.10-1.48) for those with at least 4 pregnancies after multivariate adjustment. At least 4 pregnancies through childbearing age may be a potential risk factor for diabetes in postmenopausal women without a history of gestational diabetes.

Bone metabolism and circulating myeloid calcifying cells in diabetic post menopausal women: a case-control study

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

SUN-474 Estradiol Protects Against High-Fat Diet-Induced Obesity and Anxiety in Female Mice

Menopause is characterized by a decline in ovarian function and a decrease in estrogens. This decrease in estrogens leads to changes in metabolic phenotype, increasing the risk of weight gain from fat, metabolic syndrome, and type 2 diabetes in postmenopausal women. Menopause is also associated with changes in anxiety and mood. Estradiol (E) exerts similar metabolic effects in female mice as in women. We and others have shown that ovariectomized mice fed a high-fat diet (HFD) become obese, while mice treated with E remain lean. Furthermore, in female mice, HFD increases anxiety, and E acts in specific brain regions to influence anxiety and energy metabolism. However, the mechanisms by which E and diet interact to affect anxiety in females are not well understood. The present study tested the hypothesis that E protects against HFD-induced anxiety-like behavior by altering neural activity in brain regions involved in energy regulation and anxiety. Eight-week-old C57BL6J mice were ovariectomized and implanted with capsules containing either E (50 μg E in 25 μl of 5% ETOH/sesame oil) or vehicle (V). Within each treatment group, mice were fed a standard diet (SD) for 10 days and then maintained on SD or switched to HFD for 26 more days. Mice were weighed and food intake was measured every three days. Starting on day 30, anxiety-like behavior was assessed with three behavior tests: 1) light-dark 2) open-field and 3) elevated plus maze, with an interval of 3 days between each test. To investigate the effects of HFD and E on anxiety-induced neural activity, animals were perfused after the last behavior test. Whole brains were cleared, labeled and imaged for Fos using immunolabeling-enabled three-dimensional imaging of solvent-cleared organs (iDISCO). The V mice on HFD weighed at least 32% more than all other groups on day 36, while E mice remained lean and had reduced food intake, indicating that E protects against HFD-induced obesity. HFD increased anxiety behavior in the elevated plus maze test as HFD-fed mice spent less time in the open arms (p=0.03). E reduced anxiety-like behavior in mice fed a HFD as measured by the light-dark test. E mice on HFD spent more time in the light compartment than V mice on HFD (p=0.02). E decreased anxiety-like behavior in the open-field test, as E mice entered the center zone more times than V mice (p=0.048). Interestingly, in mice fed a HFD, E decreased Fos expression in the paraventricular hypothalamic nucleus (q<0.1), bed nucleus of the stria terminalis (q<0.05), and the subparafascicular area of the thalamus (q<0.001), suggesting that E protects against HFD-induced anxiety by decreasing neural activity in these specific brain regions. These findings provide insight into the potential mechanisms by which estrogens and diet interact to regulate energy homeostasis and anxiety in postmenopausal women. Work was funded by Otsuka Pharmaceutical Development & Commercialization, Inc.

SUN-538 Osteogenic Markers in Postmenopausal Diabetics Respond to Higher Mechanical Loading during Exercise after Rather Than before the Meals

Structural integrity of bones is supported by mechanical loading, energy intake, and sex hormones. It is unclear why postmenopausal (PM) diabetics experience more bone breaks despite higher body weight and positive energy balance than non-diabetics. We hypothesized that greater bone fragility in PM diabetics may result from peripheral insulin resistance and reduced nutrient access to the bone. We engaged 15 diabetic women, age 57.7y, BMI 27.2 kg/m2, in two of five day-long experiments : SED (no exercise), UBM and UAM (40 min of uphill treadmill exercise, respectively one h before, or one h after eating two daily isocaloric meals at 10 and 17 h and containing 50% carbohydrate, 15% protein, and 25% fat), and DBM and DAM (downhill exercise at -6o slope with meals and exercise timed the same way). Markers of bone formation osteocalcin (OCN) and CICP (c-terminal propeptide of type I collagen) and of resorption, CTX (c-terminal telopeptide of type I collagen), anabolic growth hormone and catabolic cortisol were measured hourly in the serum. Glucose and insulin were measured to assess insulin resistance by the homeostatic HOMA-IR method from 7-h postprandial (PP) insulin and glucose areas under the curve (AUCs).Peak ground-reaction forces (GRFs) were monitored with Novel Pedar mechanosensitive shoe insoles, and physical effort was assessed as percent of VO2max with a metabolic cart. During uphill trials, mean effort was 75.2% , and GRFs were 780.7 N. During downhill trials, the corresponding values were 47.9% of VO2max and 1104.8 N (both >0.05). A similar CTX decline in all 5 trials after the 10h meal was larger than after the 17 h meal (7h negative PP AUCs: 1.52 vs 1.37 ng/ml*h, respectively) and coincided with PP insulin AUCs. CICP rise in DAM trial was 44% greater than in DBM trial after 10h meal (AUCs, 685.9 vs 384.1 ng/ml*h, respectively) and produced a 40 percent greater osteogenic CICP/CTX ratio after 10h meal in the in the DAM than DBM trial. No group difference was seen in brief postprandial serum glucose rises, while PP insulin was highest in UBM and SED trials and low in the two downhill and UAM trials. HOMA-IR in the two downhill trials (355.6) was reduced to 47% of that in two uphill trials (759.1) and to 62% of the SED trial (571.4). Circulating OCN and hormones showed no clear relationship to either the loading or meal-exercise timing patterns. We conclude that In PM diabetics, downhill (as opposed to uphill) exercise after a meal conveys a clear benefit in stimulating a bone- forming CICP, more so after the 10h than the 17 h meal. Meal eating, independently of exercise, lowers the bone resorption marker CTX. In diabetic PM women, Increased GRFs of downhill exercise reduce HOMA-IR insulin resistance to high-carbohydrate meals more than uphill exercise or SED control. Postprandial downhill exercise has the highest osteogenic potential.

Association Between Age at Natural Menopause and Risk of Type 2 Diabetes in Postmenopausal Women With and Without Obesity.

The relationship between age at natural menopause and type 2 diabetes mellitus (T2DM) has yielded conflicting results, particularly when confounded by the presence of obesity. We therefore aimed to examine the association between age at natural menopause and development of T2DM and the influence of postmenopausal obesity status on this association. The data for this study was derived from one center (Beijing) of the REACTION study. After screening through our inclusion and exclusion criteria, 2689 postmenopausal women who completed a 3-year follow-up were included. Logistic regression analysis was conducted to clarify the association of the age at natural menopause with the development of T2DM. After adjustment for potential confounders, there was no significant association between the age at natural menopause and development of T2DM for all subjects. However, when subjects were stratified along the postmenopausal obesity status at baseline, in the presence or absence of obesity, we found a surprising contradictory association in two subgroups: late menopause (age >50 years) was associated with an increased risk (OR, 1.45; 95% CI, 1.02 to 2.05) of developing T2DM in the postmenopausal group without obesity, whereas we found a reduced risk (OR, 0.43; 95% CI, 0.27 to 0.71) in the postmenopausal group with obesity. Moreover, we found that early menopausal women (age ≤45 years) with postmenopausal obesity had the highest risk (OR, 2.10; 95% CI, 1.11 to 4.00) of developing T2DM compared with all other postmenopausal women. Postmenopausal obesity status may influence the association of age at natural menopause and the development of T2DM.

Association between glycosylated hemoglobin A1c and bone biochemical markers in type 2 diabetic postmenopausal women: a cross-sectional study

Backgroundtype 2 diabetes mellitus (T2DM) is a complicated disease that can affect bone health, but the change in bone biochemical markers caused by T2DM was controversial, so the aim of this study was to investigate whether there was a discrepancy in the levels of bone biochemical markers between postmenopausal women with T2DM and non-diabetic women and to explore the relationship between the level of glycosylated hemoglobin A1c (HbA1c) and bone biochemical markers in these subjects.MethodsA total of 237 type 2 diabetic postmenopausal women visiting the First Affiliated Hospital of Anhui Medical University from January 2017 to October 2018 and 93 healthy postmenopausal women were retrospectively enrolled. The differences in the levels of bone biochemical markers between patients and controls were analyzed by one-way ANOVA or chi-square test. The relationship between HbA1c and bone biochemical markers was analyzed by multivariate regression, forest plot and fitted curve.ResultsBone formation markers including N-MID osteocalcin and procollagen type 1 amino-terminal pro-peptide (PINP) were decreased in postmenopausal women with T2DM compared to controls (17.42 ± 9.50 vs 23.67 ± 7.58, p < 0.001; 48.47 ± 27.27 vs 65.86 ± 21.06, p < 0.001, respectively), but the bone resorption markers β-crossLaps (β-CTX) was no difference between the two groups (0.57 ± 0.28 vs 0.55 ± 0.21, p = 0.868). Multivariate regression showed that HbA1c was inversely associated with N-MID osteocalcin and PINP after adjusting for age, BMI, menopause’s years, diabetic duration, TC, TG, HDL-c, LDL-c, creatinine, UA and eGFR. The adjusted coefficients for N-MID osteocalcin and PINP per 1% HbA1c decrease were − 0.71 (− 1.19, − 0.22) and − 1.79 (− 3.30, − 0.28), respectively. A segmentation effect was seen in the fitted curve between HbA1c and β-CTX with an inflection point at 7.4% of HbA1c, the highest quartile of β-CTX (> = 0.74 ng/ml) showed a significantly negative with HbA1c. No significant association was seen between HbA1c and other biochemical markers.ConclusionsOur study found that bone formation was inhibited in postmenopausal women with T2DM, but bone resorption was not affected, and poor glycemic control was related to lower levels of bone formation, may increase the risk of bone fracture in postmenopausal women with T2DM.